rs9061

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_080424.4(SP110):c.619G>A(p.Glu207Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 1,612,608 control chromosomes in the GnomAD database, including 9,687 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.094 ( 742 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8945 hom. )

Consequence

SP110
NM_080424.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.444

Publications

32 publications found

Variant links:

Genes affected

SP110 (HGNC:5401): (SP110 nuclear body protein) The nuclear body is a multiprotein complex that may have a role in the regulation of gene transcription. This gene is a member of the SP100/SP140 family of nuclear body proteins and encodes a leukocyte-specific nuclear body component. The protein can function as an activator of gene transcription and may serve as a nuclear hormone receptor coactivator. In addition, it has been suggested that the protein may play a role in ribosome biogenesis and in the induction of myeloid cell differentiation. Alternative splicing has been observed for this gene and three transcript variants, encoding distinct isoforms, have been identified. [provided by RefSeq, Jul 2008]

SP110 links:

SP140 (HGNC:17133): (SP140 nuclear body protein) This gene encodes a member of the SP100 family of proteins, which are share common domains including an N-terminal homogeneously staining region domain followed by a SP100/autoimmune regulator/NucP41/P75/deformed epidermal autoregulatory factor domain, a plant homeobox zinc finger, and a bromodomain. The encoded protein is interferon-inducible and is expressed at high levels in the nuclei of leukocytes. Variants of this gene have been associated with multiple sclerosis, Crohn's disease, and chronic lymphocytic leukemia. Alternative splicing results in multiple variants. [provided by RefSeq, Aug 2016]

SP140 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0052110553).

BP6

Variant 2-230212395-C-T is Benign according to our data. Variant chr2-230212395-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 334910.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP110	NM_080424.4 link	c.619G>A	p.Glu207Lys	missense_variant	Exon 5 of 19	ENST00000258381.11	NP_536349.3	Q9HB58-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP110	ENST00000258381.11 link	c.619G>A	p.Glu207Lys	missense_variant	Exon 5 of 19	2	NM_080424.4	ENSP00000258381.6		Q9HB58-6

Frequencies

GnomAD3 genomes

AF:

0.0936

AC:

14243

AN:

152122

Hom.:

741

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0757

Gnomad AMI

AF:

0.0802

Gnomad AMR

AF:

0.0654

Gnomad ASJ

AF:

0.160

Gnomad EAS

AF:

0.169

Gnomad SAS

AF:

0.238

Gnomad FIN

AF:

0.0596

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.0966

Gnomad OTH

AF:

0.0975

GnomAD2 exomes

AF:

0.111

AC:

27759

AN:

251134

AF XY:

0.118

show subpopulations

Gnomad AFR exome

AF:

0.0756

Gnomad AMR exome

AF:

0.0432

Gnomad ASJ exome

AF:

0.164

Gnomad EAS exome

AF:

0.178

Gnomad FIN exome

AF:

0.0580

Gnomad NFE exome

AF:

0.0966

Gnomad OTH exome

AF:

0.109

GnomAD4 exome

AF:

0.101

AC:

147593

AN:

1460368

Hom.:

8945

Cov.:

AF XY:

0.106

AC XY:

77078

AN XY:

726556

show subpopulations

African (AFR)

AF:

0.0808

AC:

2702

AN:

33448

American (AMR)

AF:

0.0475

AC:

2123

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.162

AC:

4224

AN:

26126

East Asian (EAS)

AF:

0.173

AC:

6846

AN:

39668

South Asian (SAS)

AF:

0.231

AC:

19870

AN:

86204

European-Finnish (FIN)

AF:

0.0597

AC:

3190

AN:

53416

Middle Eastern (MID)

AF:

0.169

AC:

975

AN:

5766

European-Non Finnish (NFE)

AF:

0.0909

AC:

100989

AN:

1110660

Other (OTH)

AF:

0.111

AC:

6674

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

6552

13104

19655

26207

32759

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3750

7500

11250

15000

18750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0936

AC:

14257

AN:

152240

Hom.:

742

Cov.:

AF XY:

0.0945

AC XY:

7038

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0762

AC:

3164

AN:

41538

American (AMR)

AF:

0.0653

AC:

999

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.160

AC:

554

AN:

3472

East Asian (EAS)

AF:

0.168

AC:

873

AN:

5186

South Asian (SAS)

AF:

0.237

AC:

1141

AN:

4824

European-Finnish (FIN)

AF:

0.0596

AC:

632

AN:

10606

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0966

AC:

6569

AN:

68002

Other (OTH)

AF:

0.0970

AC:

205

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

661

1322

1984

2645

3306

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

174

348

522

696

870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0985

Hom.:

620

Bravo

AF:

0.0899

TwinsUK

AF:

0.0930

AC:

345

ALSPAC

AF:

0.0851

AC:

328

ESP6500AA

AF:

0.0776

AC:

342

ESP6500EA

AF:

0.0938

AC:

807

ExAC

AF:

0.114

AC:

13871

Asia WGS

AF:

0.168

AC:

584

AN:

3478

EpiCase

AF:

0.0975

EpiControl

AF:

0.0985

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hepatic veno-occlusive disease-immunodeficiency syndrome

Benign:3

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

Dec 03, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

5.2

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.0014

.;T;T;.;.;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.70

T;T;T;T;T;T

MetaRNN

Benign

0.0052

T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.69

N;N;.;N;.;.

PhyloP100

-0.44

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.69

N;N;N;N;N;N

REVEL

Benign

0.053

Sift

Benign

0.20

T;T;T;T;T;T

Sift4G

Benign

0.34

T;T;T;T;T;.

Polyphen

0.049

B;B;B;.;.;.

Vest4

0.16

MPC

0.34

ClinPred

0.010

GERP RS

-4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.026

gMVP

0.25

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over